摘要
目的研究促肝细胞生长素(PHGF)对α-萘异硫氰酸酯(ANIT)致小鼠急性肝损伤的保护作用及机制,为其临床应用提供实验依据。方法 50只BALB/c雄性小鼠,随机分为对照组10只和ANIT处理组40只。ANIT处理组小鼠口服105 mg/kg ANIT后随机分为模型组、重组人肝细胞生长因子组(ANIT+rh HGF 1μg)、促肝细胞生长素低剂量组(ANIT+PHGF 10 mg/kg)、促肝细胞生长素高剂量组(ANIT+PHGF 20 mg/kg)。对照组和模型组小鼠在口服ANIT前0.5 h,口服ANIT后6,12,24,30,36 h腹腔注射生理盐水;ANIT+rh HGF 1μg组、ANIT+PHGF 10 mg/kg组和ANIT+PHGF 20 mg/kg组小鼠分别在相同时间点腹腔注射1μg rh HGF、10 mg/kg PHGF和20 mg/kg PHGF;口服ANIT后48 h,麻醉小鼠并心脏取血,血液离心后,取血清,检测谷丙转氨酶(ALT)、谷草转氨酶(AST)、碱性磷酸酶(ALP)的含量。取肝脏,部分肝脏用10%甲醛溶液固定,切片后进行HE染色,观察其病理变化;部分肝脏液氮保存,检测超氧化物歧化酶(SOD)的活性。结果 ANIT+rh HGF 1μg组、ANIT+PHGF 10 mg/kg组和ANIT+PHGF 20 mg/kg组小鼠ALT、AST、ALP含量比模型组显著降低。模型组与对照组SOD含量比较,显著增加;ANIT+rh HGF 1μg组、ANIT+PHGF 10 mg/kg组、ANIT+PHGF 20 mg/kg组与模型组SOD含量相比较,无明显差异。HE染色结果显示,ANIT+rh HGF 1μg、ANIT+PHGF 10 mg/kg和ANIT+PHGF 20 mg/kg组小鼠肝脏坏死和炎性细胞浸润情况明显减轻。结论 PHGF能保护ANIT急性小鼠肝损伤,其作用机制可能与抑制炎症反应有关。
Objective To study the protective effect and mechanism of hepatocyte growth-promoting factor （PHGF） on ANIT-indueed liver injury in mice and provide theoretical basis for its clinical use. Method Fifty male BALB/e mice were divided randomly into normal group （control group, n = 10） and ANIT treatment group （n = 40）. Liver injury model in mice was established by oral administration of ANIT（ 105 mg/kg） , recombinant human hepatocyte growth factor （rhHGF, 1 μg/miee） and 2 doses of PHGF（ 10,20 mg/kg） were administrated intraperitoneally 0.5 h before and 6,12,24,30,36 h after ANIT administration. 48 h after ANIT administration, animals were anesthetized and heart blood, the ALT, AST, ALP levels in serum and SOD level in liver tissue were detected. Furthermore, liver tissues were observed histologically by HE staining. Result ALT, AST and ALP levels in PHGF and rhHGF group were decreased significantly compared to those of the model group（P 〈 0.05）. SOD level in ANIT group was significantly higher than that in the control mice. However, there is no significant between ANIT and rhHGF, PHGF groups. Through the pathological observation, necrotic area and inflammatory cell infiltration of liver in rhHGF and PHGF group of liver cell necrosis situation was less severe than that of the model group. Conclusion PHGF can protect the ANIT-induced liver injury in mice and the mechanism of action may associated with the inhibition of inflammation
出处
《实验动物科学》
2016年第6期25-30,共6页
Laboratory Animal Science
基金
北京市教育委员会科技发展计划面上项目(No.KM201510025003)
首都医科大学基础与临床科研合作基金(No.15JL12)
关键词
促肝细胞生长素
急性肝损伤
ANIT
hepatocyte growth-promoting factor
acute liver injury
ANIT
